Р. Leu72met Mutation of Ghrelin GHRL Gene in Children With Gastroesophageal Reflux Disease

Abstract

Gastroesophageal disease (GERD) is the one of most spread diseases that injures an esophagus. Taking into account the large number of factors that can cause GERD development already in child age, including genetic predisposition, it is necessary to analyze each of them in detail. Aim of this work was to analyze a frequency and possible association type of р. Leu72Met mutation of GHRL gene in children with gastroesophageal reflux disease. The analysis of clinical parameters and course of disease in the group of 100 schoolchildren with GERD was carried out. The molecular-genetic study of c.214C>A locus of GHRL gene by CPR method (rs696217) was carried out in patients with GERD and 40 healthy children from the control group. In 82% of children with GERD was revealed a GHRL 214СС (Leu/Leu) homozygous genotype, at 58% among children from the control group. GHRL 214СА (Leu/ Met) genotype was registered three times more seldom in children of the studied group comparing with ones from the control group: 15,0% and 42,5%, respectively. It was established, that GHRL 214CС genotype presence conditions the increase of GERD development risk in 3,4 times. On the contrary, GHRL 214CА genotype manifests a reliable protective effect that is essentially decreased GERD development risk in a child at such genotype – 0,24 comparing with a conventional unit. There was established alleles and genotypes distribution of c.214C>A (р.Leu72Met) locus of GHRL gene in children with GERD. GHRL 214CС genotype is associated with threefold increase of GERD risk development. Gender differences as to GERD development risk at different genotypes of ghrelin gene were established. At GHRL 214СС (Leu/Leu) genotype the relative GERD risk for boys increased in more than 6 times. There were not established any differences in alleles and genotypes distribution depending on erosive or surface inflammatory changes of a gastrointestinal tract mucosa.

Ghrelin Gene Polymorphisms in Irritable Bowel Syndrome

“…Our results are partly in agreement with a previous study by Russo et al [22] that reported a reduction of both the rs696217 GT genotype and the T allele in IBS-D patients, given that when we classified our patients according to IBS subtype, no statistically significant differences were observed for any of the polymorphisms tested. Our results regarding rs696217 are in agreement with the previous study on GERD by Dats-Opoka et al [23]. Regarding the rs34911341 and rs2075356 polymorphisms, no statistically significant association with IBS was observed in this present study.…”

“…Recently, Russo et al [22] suggested that the GT genotype and the T allele of the GHRL rs696217 polymorphism were reduced in IBS-D patients compared to healthy individuals (HC), but only a small number of IBS-D only patients and controls were tested in this study. Additionally, Dats-Opoka et al [23] supported that the rs696217 GG genotype is associated with a threefold increase in risk for GERD development in children. Therefore, since the relative information is currently limited, in the present study, we examined the association between the risk of IBS and certain GHRL gene polymorphisms in a well-characterized cohort of Greek IBS patients.…”